Intrahypothalamic secretion of angiotensin II in response to immunological or non-immunological stress in rats : a microdialysis study

我们以前曾报道，脑血管紧张素II（ANG II）受体参与大鼠免疫或非免疫应激引起的发热。本研究应用微透析技术，观察了免疫应激（注射前列腺素E_2）和非免疫应激（制动）对大鼠下丘脑血管紧张素Ⅱ（ANG Ⅱ）分泌的影响。我们的微透析研究（灌流流速=2 μl/min，回收率=14.2%）表明，在下丘脑灌注PGE_2（2 μg/2 μl灌流液/min）时，下丘脑中ANG Ⅱ的释放可通过灌流液中少量ANG Ⅱ的存在来检测（平均为0.17 pg/2 μl灌流液/min ; n=3）。ANG II的这种释放在载体输注期间没有发生（n=4）。下丘脑PGE_2与下丘脑内PGE受体结合，导致ANG Ⅱ释放。下丘脑释放的ANG Ⅱ可能参与PGE_2致热反应的调节。相反，当大鼠暴露于束缚应激时，在大鼠的下丘脑中没有检测到ANG II的分泌。由于本研究中使用的微透析探针的回收率为14.2%，并且肽非常不稳定，因此可能无法测量ANG II的实际分泌。需要技术改进来检测如此少量的肽，例如通过使用使肽失活的酶的抑制剂。

We previously reported that brain angiotensin II (ANG II) receptors contribute to the fever induced by immunological or non-immunological stress in rats. The present study was carried out to investigate whether immunological [prostaglandin E_2 (PGE_2) injection] or non-immunological (immobilization) stress elicits the secretion of ANG II in the hypothalamus in rats, using microdialysis technique. Our microdialysis study (perfusion flow rate=2 μl/min and recovery rate=14.2%) showed that, during intrahypothalamic perfusion with PGE_2 (2 μg/2 μl perfusate/min), ANG II release in the hypothalamus could be detected by the presence of a small amount of ANG II in the perfusate (on average, 0.17 pg/2 μl perfusate/min ; n=3). Such a release of ANG II did not occur during vehicle infusion (n=4). It is therefore reasonable to consider that PGE_2 in the hypothalamus binds to intrahypothalamic PGE receptors, which results in ANG II release. Subsequently, ANG II released within the hypothalamus might modulate the PGE_2-induced febrile responses. In contrast, when rats were exposed to immobilization stress, no secretion of ANG II was detected in the rat's hypothalamus. Since the recovery rate of the microdialysis probe used in this study was 14.2% and the peptide is so unstable, actual secretion of ANG II might have been unable to be measured. Technical improvement is necessary to detect such a small amount of the peptide, for example by using the inhibitors of the enzyme which inactivates the peptide.